Cutting Edge: Overlapping Functions of TLR7 and TLR9 for Innate Defense against a Herpesvirus Infection

• Published in: The Journal of immunology (1950) Vol. 180; no. 9; pp. 5799 - 5803
• Main Authors: Zucchini, Nicolas, Bessou, Gilles, Traub, Stephanie, Robbins, Scott H, Uematsu, Satoshi, Akira, Shizuo, Alexopoulou, Lena, Dalod, Marc
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.05.2008; Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists
• Subjects: Animals; Dendritic Cells; Dendritic Cells - immunology; Herpesviridae Infections; Herpesviridae Infections - genetics; Herpesviridae Infections - immunology; Herpesvirus; Immunity, Innate - genetics; Immunity, Natural; Immunology; Interferon-alpha; Interferon-alpha - genetics; Interferon-alpha - immunology; Interferon-beta; Interferon-beta - genetics; Interferon-beta - immunology; Interleukin-12 Subunit p40; Interleukin-12 Subunit p40 - genetics; Interleukin-12 Subunit p40 - immunology; Life Sciences; Membrane Glycoproteins; Membrane Glycoproteins - genetics; Membrane Glycoproteins - immunology; Mice; Mice, Knockout; Murine cytomegalovirus; Muromegalovirus; Muromegalovirus - immunology; Myeloid Differentiation Factor 88; Myeloid Differentiation Factor 88 - genetics; Myeloid Differentiation Factor 88 - immunology; Toll-Like Receptor 7; Toll-Like Receptor 7 - genetics; Toll-Like Receptor 7 - immunology; Toll-Like Receptor 9; Toll-Like Receptor 9 - genetics; Toll-Like Receptor 9 - immunology; Tumor Necrosis Factor-alpha; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - immunology; Viral Load
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.180.9.5799

As initially demonstrated with murine cytomegalovirus (MCMV), plasmacytoid dendritic cells (pDCs) are the major source of IFN-α/β in response to a variety of viruses in vivo. However, contradictory results have been obtained pertaining to the mechanisms promoting IFN-α/β production by pDCs in response to MCMV. In this study we show that TLR7 and TLR9 exert redundant functions for IFN-α/β, IL-12p40, and TNF-α production by pDCs in vivo during MCMV infection. In contrast, we confirm that systemic production of IL-12p70 strictly depends on TLR9. The combined loss of TLR7 and TLR9 recapitulates critical features of the phenotype of MyD88-deficient mice, including a dramatic decrease in systemic IFN-α/β levels, an increase in viral load, and increased susceptibility to MCMV-induced mortality. This is the first demonstration of the implication of TLR7 in the recognition of a DNA virus.